By monitoring the highly specific proteomic "fingerprints" of autoantibody
responses, a multi-disciplinary team from the Stanford University School
of Medicine selected and then, tested disease- and patient-specific DNA
"cocktails" in experimental autoimmune encephalomyelitis (EAE), a model
for multiple sclerosis (MS), demonstrating the effectiveness of these novel
therapeutics in reducing epitope spreading of autoreactive B cell responses.
In an article published in the September issue of Nature Biotechnology,
senior author Lawrence Steinman, M.D., Professor of Neurology and Neurological
Sciences, Stanford University indicated that "epitope spreading" -- the
expansion of the immune response beyond the initial target of attack --
is considered by many experts to be an essential step in the cascade that
results in autoimmune disease, and opined that "through 'reverse genomics,'
(the authors' approach could be used) to develop and tailor disease- and
patient-specific tolerizing DNA vaccines for autoimmune diseases."

The research represents what the authors describe as "an integrated
approach to treat autoimmune disease using proteomic analysis of the specificity
of autoantibody responses to guide development of genetic tolerizing vaccines."
The team developed antigen microarrays containing up to 2323 distinct antigens
to study the evolution of B cell responses in EAE. Based on that information,
the team concluded that the diversity of autoreactive B cell responses
in acute EAE was predictive of disease severity, and created DNA cocktails
encoding multiple array-determined myelin targets to improve clinical outcomes.
As compared to control therapies, the relapse rate of animals treated with
DNA cocktail alone or DNA cocktail plus IL-4 was significantly reduced.

Both MS and EAE, the experimental model of MS, include a relapsing-remitting
pattern of disease activity, with periodic exacerbations of neurologic
dysfunction that frequently lead to accumulating disability. The authors
noted that epitope spreading may actually drive clinical relapses in the
disease and the model, suggesting that the high sensitivity of their antigen
arrays was responsible for improved understanding of the diversity and
the specificity of the autoreactive B cell response, and these observations
provided a strong foundation of knowledge upon which a new generation of
DNA therapeutics for autoimmune disease can be developed. This work they
said, "has the potential to revolutionize care for patients with autoimmune
diseases by enabling identification of 'biosignatures' for diagnosis, prognostication,
and guiding tolerizing therapy."

The Steinman et al. approach is the basis of much of the work at Palo
Alto, CA-based Bayhill Therapeutics, a company focused on translating promising
research in autoimmune disease into commercialized therapeutics. The company
has established a therapeutic platform of autoimmune modulators, in-licensed,
from Stanford University, as well as proprietary combination modulators.
Dr. Steinman, along with William Robinson, M.D., Ph.D., of the Department
of Neurology and Neurological Sciences at Stanford University; Hideki Garren,
M.D., Ph.D., Director of Immunology and Molecular Biology at Bayhill; and
Paul J. Utz, M.D., Assistant Professor of Medicine, Rheumatology and Immunology
at Stanford University; founded the company. To date, Bayhill Therapeutics
has demonstrated proof-of-concept with these antigen specific therapies
(AIMTx(TM)), as well as in combination with two of more autoimmune modulators
(AIM(TM)) in the EAE model of multiple sclerosis, the NOD model of insulin-dependent
diabetes mellitus and the collagen-induced arthritis model of rheumatoid
arthritis. The Company plans to enter clinical studies in the first half
of 2004 with an antigen specific therapy (AIMTx(TM)) for the treatment
of MS. As part of the clinical outcomes measures Bayhill intends to monitor
the antibody responses correlated in the EAE work published in Nature Biotechnology.

About Bayhill Therapeutics, Inc.

Bayhill Therapeutics Inc. is focused on the translation of research
into therapeutics for the treatment of autoimmune diseases. The company
has established a therapeutic platform of autoimmune modulators, in-licensed
from Stanford University, that address the broad market of Th1 mediated
autoimmune diseases. The Company's initial disease focus is multiple sclerosis,
with its first product (BHT- 3009) entering Phase I/II studies in the first
quarter of 2004. In addition, the Company has a strong portfolio of product
programs focused around individual agents with demonstrated proof of concept
as autoimmune modulators (AIM(TM)), as well as in the combination of these
modulators in a proprietary manner, AIMTx(TM).

More information on Bayhill Therapeutics Inc. can be found at www.bayhilltherapeutics.com.